Generally in normal bone metabolism, bone resorption by osteoclasts and osteogenesis by osteoblasts are balanced, whereby homeostasis is maintained. It is presumed that diseases associated with bone metabolism develop when the balance between bone resorption and osteogenesis is disrupted. Such diseases include osteoporosis, osteitis fibrosa (hyperparathyroidism), osteomalacia, Paget's disease, and the like. Particularly, osteoporosis often develops in postmenopausal women and elderly people with accompanying symptoms of pain such as low back pain, bone fracture, etc. Particularly, bone fracture in elderly people is serious because it leads to generalized weakness and dementia. For such diseases associated with bone metabolism, hormone replacement therapies with estrogen and therapeutic agents such as bisphosphonates and calcitonins, both of which inhibit the activity of osteoclasts, have been employed.
However, although many of these therapeutic agents are reported to have a bone resorption-inhibiting action, etc., none of them has yet been clearly shown to have an osteogenesis-promoting action. Particularly, impaired osteogenic ability due to reduced bone turnover is reported to be the main cause of senile osteoporosis (Non Patent Reference 1), and thus a medicinal agent promoting osteogenesis is considered to be effective.
In view of the above, development of a highly clinically effective, orally administrable osteogenesis promoter is demanded.
Recently, benzothiepine derivatives having an alkaline phosphatase-inducing activity (Patent References 1 and 2), N-quinolylanthranilic acid derivatives (Patent Reference 3), triazolopyridazine derivatives (Patent Reference 4), and thienopyridine derivatives (Patent Reference 5) are reported to be useful for promotion of osteogenesis and for the treatment of diseases associated with bone metabolism. However, their clinical utility remains unknown.